The influenza virus haemagglutinin (HA) glycoprotein is being studied as a prototype membrane surface antigen. X-ray crystallographic, Electron microscopic, and biochemical studies are proposed to investigate the functions of this protein on the viral membrane surface, and to learn how those functions contribute to recurrent epidemics in man. How the virus binds to a target cell is being studied by X-ray structural studies of wild type and mutant HAs with altered receptor specificities, complexed with receptor analogs and receptor fragments. The mechanism of membrane fusion mediated by the HA to effect viral penetration into a host cell is being studied by X-ray studies of a fusion inactive precursor HAO, by crystallization studies of protein-detergent complexes and EM image analysis of the hydrophobic, fusion-active HA conformation, and by calculations and modifications on mutant HAs. The interaction of the HA with molecules of the human immune system is being studied by structural studies of antigenic variants, both monoclonal antibody selected and natural. This includes the production of novel antigenic types by molecular cloning. Attempts will be made to crystallize an antibody-antigen complex suitable for X-ray analysis.